骨髓间充质干细胞移植治疗大鼠糖尿病心肌病的初步研究  

The effect of bone marrow mesenchymal stem cell transplantation on diabetic cardiomyopathy

作　　者：张楠[1] 李佳慧[2] 王建安[3] 张鸿坤[4] 

机构地区：[1]浙江大学医学院附属邵逸夫医院内分泌科,杭州310016 [2]北京中日友好医院心内科 [3]浙江大学医学院附属第二医院心内科 [4]浙江大学医学院附属第一医院血管外科

出　　处：《中华心血管病杂志》2008年第12期1115-1119,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30700300）;浙江省医药卫生科技项目（2007A120）

摘　　要：目的探讨骨髓间充质干细胞移植对糖尿病心肌病心功能的影响及其可能的机制。方法采用链脲佐菌素（STZ）建立糖尿病大鼠模型，骨髓间充质干细胞（MSC）从雄性SD大鼠的胫腓骨获取并培养，在体外用DAPI标记后，股静脉回输。4周后在对照组，糖尿病心肌病组（DCM组）及移植组（MSC组）间经心脏超声、免疫荧光、免疫组化及PT—PCR方法分析金属基质蛋白酶（MMP）-2、MMP-9及组织型金属基质蛋白酶抑制剂（TIMP）mRNA的表达，并分析MMP-2的蛋白活性，Westernblot法分析肌钙蛋白T（cTnT）表达。结果DCM组左心室后壁厚度（LVPW）和心肌动脉密度低于对照组（t=4．35，P〈0．01），MSC组高于DCM组（t=4．86，P〈0．05）。DCM组TIMP-1mRNA和MMP-2活性低于对照组（t=3．67，P〈0．01），MSC组高于DCM组，但仅MMP-2活性差异有统计学意义（t=3．42，P〈0．01）。结论经静脉移植MSC能诱导血管的新生，诱导MMP及TIMP的表达，改善心肌重构，但不足以影响射血分数。Objective Diabetic cardiomyopathy （DCM）, an important cause of heart failure, is characterized by microvascular pathologies and interstitial fibrosis. Bone marrow mesenchymal stem cells （MSCs） are pluripotent, which can differentiate into cardiomyocytes and vascular endothelial cells. They also secrete angiogenic and antiapoptotic factors. However, little information is available about the effect of MSCs transplantation on diabetic heart. Methods MSCs were isolated from bone marrow of isogenic adult rats and cultured ex vivo. Eight weeks post streptozotocin injection, saline or exogenous MSCs labelled with 4＇6-Diamidino-2-Phenylindole （DAPI） were injected into the femoral vein of diabetic rats and examined 4 weeks later by echocardiography, histopathologic analysis, reverse transcription polymerase chain reaction analysis for matrix metalloproteinase （MMP）-2, MMP-9 and tissue inhibitor of matrix metalloproteinase （TIMP）-1, zymography analysis for activites of MMP-2 and Western blot analysis for troponin T. Results Left ventricular posterior wall thickness and myocardial arteriolar density as well as the TIMP-1 mRNA and MMP-2 activity were significantly decreased in DCM group （P 〈 0. 01 versus control group respectively）, these changes were significantly attenuated by MSCs transplantation （ P 〈 0. 05 versus DCM ） . MSCs transplantation also significantly reduced fibrosis and downregulated MMP-9 mRNA in diabetic myocardium. Conclusion Intravenous MSCs transplantation could attenuate LV remodeling in DCM rats.

关 键 词：糖尿病 心肌疾病 干细胞移植 基质金属蛋白酶类 

分 类 号：R686[医药卫生—骨科学]